There are a number of ophthalmic musculoskeletal and nerve surgical procedures performed by skilled surgeons which require or are facilitated by the use of a viscoelastic medium. Among these are cataract surgery, vitreo-retinal surgery, radial keratomtomy to reduce myopia, arthroscopic surgery, urologic surgery, joint surgery, plastic surgery, and wound adhesion prevention.
In all of the ophthalmic surgical procedures except for radial keratotomy, in which the corneal tissue is not fully penetrated, the recommended practice is to use an intraocular viscoelastic fluid for protecting the inner endothelial corneal surface and the delicate inner eye structures.
In addition, the outer epithelial surface of the cornea must be lubricated continuously with some type of hydrating agent to keep it from drying out under the heat generated by the operating microscope light.
Methylcellulose has a long history of safe and effective use for ophthalmic applications. In 1945, Dr. Kenneth C. Swan studied the effects of methycellulose on the ocular tissues of rabbit eyes. He suggested its use as a vehicle for ophthalmic drugs, to treat keratoconjunctivitis sicca and as an emollient. Then in 1959, Flemming, Merrill and Girard reported on further studies of methylcellulose in relation to irritation, hypersensitivity and its outflow from the anterior chamber of the rabbit eye.
The first reported use of methycellulose as an intraocular lens coating serving to protect the corneal endothelium in rabbits was made by Drs. Kaufman and Katz in 1976. In the following year, Dr. Paul Fechner reported upon the first human clinical use of methylcellulose to coat an intraocular lens prior to implantation.
Then in November 1982, Dr. Danielle Aron-Rosa reported using methycellulose in extracapsular surgery instead of high molecular weight sodium hyaluronate extracted from rooster combs which is very expensive. Shortly thereafter, Dr. Fechner amplified upon his earlier findings describing the use of methycellulose as in intraocular viscous cushioning material in ophthalmic surgery.
Additional work confirming these earlier results has been conducted by Dr. Scott M. MacRae who compared the efficacy and toxicity of sodium hyaluronate, methylcellulose and chondroitin sulfate, all three of which are used as protective substances suitable for use in ophthalmic surgery. Finally, Drs. Smith and Lindstrom evaluated the safety and efficacy of 2% methylcellulose in cat and monkey implant surgery with favorable results.
As already noted, the use of methycellulose derivatives as protective cushioning materials to protect the inner eye structures during ophthalmic surgery is old and well known. On the other hand, use of methylcellulose as one ingredient of a topical surgical solution which, in a more dilute form, is used to keep the corneal tissues moist as an adjunct to surgery is, once again, so far as applicant is aware, heretofore unknown in the art although it is, of course, used as an ingredient in so-called "artificial tears" for treating dry eyes and as a component of contact lens solutions.
The closest and most pertinent prior art known to application is contained in two U.S. Patents, specifically, U.S. Pat. No. 4,500,538 issued Feb. 19, 1985 to Otto W. Woltersdorf under the title of "Benzothiazolesulfonamide Derivatives for the Topical Treatment of Elevated Intraocular Pressure" and Irving Katz U.S. Pat. No. 4,287,175 issued Sept. 1, 1981 for "Contact Lens Wetting Agents", both of the aforementioned patents being assigned to Merck & Co., Inc. The earlier Katz patent teaches the use of hydroxypropylmethyl cellulose or polyethylene oxide among other polymeric viscosity building agents as a solid water soluble insert as a wetting agent for contact lens wearers or so-called "artificial tears". These wetting agents are, however, used in solid form and, as such, are totally unsuitable for use in hydrating and protecting the delicate epithelial cells in ophthalmic surgery. Moreover, there is no suggestion that they be used together or that any useful result whatsoever would be achieved by so doing. As a matter of fact, the elastic properties of the two in combination, for that matter, either one alone, is not a factor in their use as wetting agents.
The Woltersdorf patent also mentions the use of hydroxypropylmethyl cellulose and polyethylene oxide as solid water soluble carriers for the active medicament of the invention, namely, the carbonates of 6 or 5-hydroxy-2-benzothiazoe-sulfonamide for use in the reduction of elevated intraocular pressure of the type often associated with glaucoma. Here again, these high molecular weight substances are used merely as a base for the active ingredient when used as a solid insert as opposed to a solution administered in the form of drops. There is no mention of them being used together nor is their elastic property of any consequence in this application. Most significant, however, is that the formulation of the Woltersdorf patent would be unsuitable for use as a viscoelastic coating to protect the delicate inner eye surfaces during ophthalmic surgery or, for that matter, as a topical moisturizing agent to be used during such surgery as long-lasting moisturizing agent.
In arthroscopy the surgeon visualizes the inside of a joint through a small diameter endoscope inserted into the joint through a 2 mm incision. The joint may be operated upon through similar incisions using fiber optic light systems along with miniaturized hand and motorized instruments.
Diagnostic arthroscopy is currently being used in temporomadibular, shoulder, elbow, wrist, finger, hip and ankle joints. Surgical arthroscopic procedures include synovectomy, chondroplasty, removal of loose bodies and resection of scar tissue.
During the surgical procedures a copious flow of saline solution is used to maintain a clear surgical field. Intense, magnified light is directed into the surgical area through fiber optic light bundles. During surgery, the surgeon is assisted by a well trained technician. The technician helps to position the extremity, controls the irrigation system and hands instruments to the surgeon. Up to six liters of saline solution may be used during the procedure. The joint area is vacuumed to remove loose bodies and bloody synovial debris. Copious fluid flow and contact by the instruments to the bone may contribute to tissue damage and post surgical inflammation.
Modifications of sodium hyaluronate or hyaluronic acid are being developed to be used arthroscopic surgery to enhance visualization, and control bleeding; to be used as a post surgical joint lubricant to replace synovial fluid; and to be injected into joints to treat pain caused by arthritis. (Private Placement Memorandum for Biomatrix, Inc. by BNE Associates, June 14, 1988.)
Spinal laminectomies are performed when disc material extrudes from the spinal column, putting pressure on nerves, causing low back pain. The remedy is to remove the offending disc material. However, in nearly 70% of all spine surgery, while the surgery is successful, the pain is not eliminated and the patient suffers from "failed back syndrome". The cause for this failure is postulated to be scar tissue formation around the dura and nerve roots. Adhesions cause pressure and friction resulting in pain.
Methycellulose and methycellulose derivatives are known to reduce the formation of adhesions and scarring that may develop following surgery. (Thomas E. Elkins M.D., et al., "Potential for In-Vitro Growth Bacteria in Solutions of 32% Dextran 70 to 10% Sodium Carboxymethycellulose" Fertility and Sterility, Vol. 43, #3, Mar. 1985; Thomas E. Elkins M.D., et al., "Adhesion Prevention by Solutions of Sodium Carboxymethylcellulose in The Rat, Part I", Fertility and Serility, Vol. 41, #6, June 1984; Thomas E. Elkins M.D., et al., "Adhesion Prevention by Solutions of Sodium Carboxymethylcellulose in The Rat, Part II", Fertility and Serility, Vol. 41, #6 1984; C. M. Fedricks Ph.D., et al., "Adhesion Prevention The Rabbit with Sodium Carboxymethylcellulose Solutions", American Journal of Obstetrics and Gynecology, 1986; 1ss; 667.70).
Indwelling urinary catheters can be difficult to remove and the process painful to the patient. Mucous membranes tend to dry around the hydrophobic catheter. A dry coating which becomes slippery and stays hydrated would facilitate removal of catheters.
Urologic surgery is similar to arthroscopic surgery in the use of endscopic instruments, lights and large amounts of sterile saline operating fluids. Indeed, many of the techniques and devices of arthroscopy were derived from urologic procedures.
Implantable silicone prostheses are commonly used in plastic surgery. The silicone implants now on the market are filled with silicone gel or a saline solution. Saline solutions lack viscosity and in the event of implant rupture, they quickly lose their volume and shape. Silicone gel has been shown to permeate the silicone shell membrane with the result that the silicone fluid collects within the body. Silicone fluids are not broken down and excreted by the body and may cause adverse effects such as scleroderma. Post surgically, the body forms a scar around all silicone implants in a process known as capsular contracture. In mammary augmentation, this process results in firm, hard upraised breasts. The scar must be broken to restore a "natural" breast line. Adhesion formation is common with types of silicone implants.
U.S. Pat. No. 4,042,978 to Jones et al. discloses the use of polyethylene oxide in a rigid plastic implantable prosthetic device.
Despite the high cost of viscoelastic products based upon sodium hyaluronate, all commercially available ones in common use have it as the sole or at least principal ingredient. Some manufacturers of viscoelastic materials have developed a bioengineered form of sodium hyaluronate but so far it appears that efforts at producing it with a sufficiently high molecular weight have been only marginally successful. A polyacrylamide based viscoelastic material is evidently being tested.